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      Hsp104-dependent ability to assimilate mannitol and sorbitol conferred by a truncated Cyc8 with a C-terminal polyglutamine in Saccharomyces cerevisiae

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          Abstract

          Tup1-Cyc8 (also known as Tup1-Ssn6) is a general transcriptional corepressor. D-Mannitol (mannitol) and D-sorbitol (sorbitol) are the major polyols in nature. Budding yeast Saccharomyces cerevisiae is unable to assimilate mannitol or sorbitol, but acquires the ability to assimilate mannitol due to a spontaneous mutation in TUP1 or CYC8. In this study, we found that spontaneous mutation of TUP1 or CYC8 also permitted assimilation of sorbitol. Some spontaneous nonsense mutations of CYC8 produced a truncated Cyc8 with a C-terminal polyglutamine. The effects were guanidine hydrochloride-sensitive and were dependent on Hsp104, but were complemented by introduction of CYC8, ruling out involvement of a prion. Assimilation of mannitol and sorbitol conferred by other mutations of TUP1 or CYC8 was guanidine hydrochloride-tolerant. It is physiologically reasonable that S. cerevisiae carries this mechanism to acquire the ability to assimilate major polyols in nature.

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          Getting started with yeast.

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            Prions are a common mechanism for phenotypic inheritance in wild yeasts.

            The self-templating conformations of yeast prion proteins act as epigenetic elements of inheritance. Yeast prions might provide a mechanism for generating heritable phenotypic diversity that promotes survival in fluctuating environments and the evolution of new traits. However, this hypothesis is highly controversial. Prions that create new traits have not been found in wild strains, leading to the perception that they are rare 'diseases' of laboratory cultivation. Here we biochemically test approximately 700 wild strains of Saccharomyces for [PSI(+)] or [MOT3(+)], and find these prions in many. They conferred diverse phenotypes that were frequently beneficial under selective conditions. Simple meiotic re-assortment of the variation harboured within a strain readily fixed one such trait, making it robust and prion-independent. Finally, we genetically screened for unknown prion elements. Fully one-third of wild strains harboured them. These, too, created diverse, often beneficial phenotypes. Thus, prions broadly govern heritable traits in nature, in a manner that could profoundly expand adaptive opportunities.
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              A systematic survey identifies prions and illuminates sequence features of prionogenic proteins.

              Prions are proteins that convert between structurally and functionally distinct states, one or more of which is transmissible. In yeast, this ability allows them to act as non-Mendelian elements of phenotypic inheritance. To further our understanding of prion biology, we conducted a bioinformatic proteome-wide survey for prionogenic proteins in S. cerevisiae, followed by experimental investigations of 100 prion candidates. We found an unexpected amino acid bias in aggregation-prone candidates and discovered that 19 of these could also form prions. At least one of these prion proteins, Mot3, produces a bona fide prion in its natural context that increases population-level phenotypic heterogeneity. The self-perpetuating states of these proteins present a vast source of heritable phenotypic variation that increases the adaptability of yeast populations to diverse environments.
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                Author and article information

                Contributors
                Role: Investigation
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Funding acquisitionRole: InvestigationRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                11 November 2020
                2020
                : 15
                : 11
                : e0242054
                Affiliations
                [1 ] Laboratory of Basic and Applied Molecular Biotechnology, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan
                [2 ] Faculty of Science and Engineering, Department of Life Science, Setsunan University, Ikeda-Nakamachi, Neyagawa, Osaka, Japan
                [3 ] Laboratory for Environmental Biotechnology, Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Suematsu, Nonoichi, Ishikawa, Japan
                University of Parma, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-3640-9540
                Article
                PONE-D-20-21750
                10.1371/journal.pone.0242054
                7657529
                33175887
                fb6ea9dd-5dd6-486e-b19d-c3ec1b09ea0d
                © 2020 Tanaka et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 July 2020
                : 27 October 2020
                Page count
                Figures: 3, Tables: 2, Pages: 12
                Funding
                Research Grant-in-Aid (to S.K.) from the 41th Iwatani Naoji Foundation Iwatani Scientific Technology ( http://www.iwatani-foundation.or.jp/) Research Grant-in-Aid in 2015 (to S.K.) from Shorai Foundation for Science And Technology ( https://www.harima.co.jp/en/shorai-foundation/) Research Grant-in-Aid in 2015 (to S.K.) from Asahi Group foundation ( http://www.asahigroup-foundation.com/academic/) Grant-in-Aid for Scientific Research (C) (19K05796) (to S.K.) ( https://www.jsps.go.jp/english/e-grants/) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Research and Analysis Methods
                Animal Studies
                Experimental Organism Systems
                Model Organisms
                Saccharomyces Cerevisiae
                Research and Analysis Methods
                Model Organisms
                Saccharomyces Cerevisiae
                Biology and Life Sciences
                Organisms
                Eukaryota
                Fungi
                Yeast
                Saccharomyces
                Saccharomyces Cerevisiae
                Research and Analysis Methods
                Animal Studies
                Experimental Organism Systems
                Yeast and Fungal Models
                Saccharomyces Cerevisiae
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Alcohols
                Mannitol
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Alcohols
                Mannitol
                Biology and Life Sciences
                Genetics
                Mutation
                Nonsense Mutation
                Physical Sciences
                Physics
                States of Matter
                Fluids
                Liquids
                Biology and Life Sciences
                Organisms
                Eukaryota
                Fungi
                Yeast
                Biology and Life Sciences
                Genetics
                Mutation
                Substitution Mutation
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Gene Expression and Vector Techniques
                Hyperexpression Techniques
                Research and Analysis Methods
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Gene Expression and Vector Techniques
                Hyperexpression Techniques
                Biology and Life Sciences
                Genetics
                Genomics
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

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